RESUMEN
BACKGROUND: Lung alveolarization, the development of the alveoli, is disturbed in preterm infants with bronchopulmonary dysplasia (BPD), the most common complication of preterm birth. Animal models based on oxygen toxicity to the developing mouse lung are used to understand the mechanisms of stunted alveolarization in BPD, and to develop new medical management strategies for affected infants. The toxicity of genetic and pharmacological interventions, together with maternal cannibalism, reduce mouse litter sizes in experimental studies. The impact of litter size on normal and stunted lung alveolarization is unknown, but may influence data interpretation. The aim of the study was to assess the impact of litter size on normal and oxygen-stunted lung alveolarization in mice. METHODS: BPD was experimentally modelled in newborn C57BL/6J mice by exposure to 85% O2 in the inspired air for the first 14 days of post-natal life. Perturbations to mouse lung architecture were assessed by design-based stereology, in which the alveolar density, total number of alveoli, gas-exchange surface area, and the septal thickness were estimated. RESULTS: Litter sizes of a single mouse were not viable to post-natal day 14. Normal lung alveolarization was comparable in mouse pups in litters of 2, 4, 6, and 8 pups per litter. Hyperoxia was equally effective at stunting lung alveolarization in mouse pups in litters of 2, 4, 6, and 8 pups per litter. CONCLUSIONS: Studies on normal lung alveolarization as well as alveolarization stunted by oxygen toxicity can be undertaken in mouse litters as small as two pups, and as large as eight pups. There is no evidence to suggest that data cannot be compared within and between litters of two to eight mouse pups.